Certain therapeutic nucleosides are known in the art. For example, certain modified nucleosides possess antiviral activity. For example, certain such nucleosides inhibit viral polymerases, such as Hepatitis C Virus (HCV) NS5b polymerase. See e.g., U.S. Pat. No. 7,105,499.
In certain instances, certain chemical moieties, when attached to a parent compound, enhance entry of such parent compound into a cell. In certain such instances, entry is particularly increased for a particular cell type. For example, it has been reported that N-acetyl galactoseamine (GalNAc), when attached through certain linkers to an siRNA compound can increase uptake of such siRNA compound into liver cells.
Antisense compounds have been described previously. The principle behind antisense technology is that an antisense compound hybridizes to a target nucleic acid and modulates the amount, activity, and/or function of the target nucleic acid. For example in certain instances, antisense compounds result in altered transcription or translation of a target. Such modulation of expression can be achieved by, for example, target mRNA degradation or occupancy-based inhibition. An example of modulation of RNA target function by degradation is RNase H-based degradation of the target RNA upon hybridization with a DNA-like antisense compound. Another example of modulation of gene expression by target degradation is RNA interference (RNAi). RNAi refers to antisense-mediated gene silencing through a mechanism that utilizes the RNA-induced silencing complex (RISC).
Chemical modifications increasing potency of therapeutic nucleosides and/or antisense compounds allow administration of lower doses, which reduces the potential for toxicity, as well as decreasing overall cost of therapy.